Impact of renal denervation on quality of life (How does renal denervation contribute to improving hypertension treatment affected by poor medication adherence?).

The US Food and Drug Administration has approved renal denervation (RDN) as a new treatment option for hypertension (HT) because it not only has antihypertensive effects but also improves the quality of blood pressure (BP) reduction. RDN is expected to be increasingly used in clinical practice in the future. This review summarizes the impact of RDN on quality of life (QOL). Although the treatment of HT aims to improve life prognosis, the use of antihypertensive agents can impair QOL because of adverse effects and lifestyle changes associated with long-term medication use. Consequently, poor adherence to antihypertensive agents is a common problem and may be the most important issue affecting patient QOL. In RDN trials in patients taking antihypertensive agents, approximately 40% of patients had poor adherence to the drugs. Poor adherence is often the cause of resistant hypertension. Therefore, RDN should be well suited to treating HT and improving QOL. Studies have shown that approximately 30% of HT patients prefer RDN to drug treatment. Patients who prefer RDN are typically male and younger and have high BP, poor adherence, and a history of adverse effects of antihypertensive agents. We hope that RDN will improve not only life prognosis but also QOL in HT patients because of its benefits for adherence. Furthermore, we expect that in the future, RDN will be used in other sympathetic nervous system-related diseases, such as heart failure, atrial fibrillation, and sleep apnea syndrome.

A case report of perihilar cholangiocarcinoma in a patient with situs inversus totalis.

Situs inversus totalis is a rare congenital malformation in which organs are positioned in a mirror-image relationship to normal conditions. It often presents with vascular and biliary malformations. Only a few reports have pointed out the surgical difficulties in patients with situs inversus totalis, especially in those with perihilar cholangiocarcinoma. This report describes a 66-year-old male patient who underwent left hemihepatectomy (S5, 6, 7, and 8) with combined resection of the caudate lobe (S1), extrahepatic bile duct, and regional lymph nodes for perihilar cholangiocarcinoma with situs inversus totalis. Cholangiocarcinoma was mainly located in the perihilar area and progressed extensively into the bile duct. Surgery was performed after careful evaluation of the unusual anatomy. Although several vascular anomalies required delicate manipulation, the procedures were performed without major intraoperative complications. Postoperatively, bile leakage occurred, but the patient recovered with drainage treatment. The patient was discharged on the 29th postoperative day. Adjuvant chemotherapy with S-1 was administered for approximately 6 months. There was no recurrence 15 months postoperatively. Appropriate imaging studies and an understanding of unusual anatomy make surgery safe and provide suitable treatment for patients with situs inversus totalis.

Skeletal muscle mass and function are affected by pancreatic atrophy, pancreatic exocrine insufficiency and poor nutritional status in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVE: Previous studies have demonstrated that sarcopenia is frequently observed in patients with chronic pancreatitis (CP). However, most studies have defined sarcopenia solely based on skeletal muscle (SM) loss, and muscle weakness such as grip strength (GS) reduction has not been considered. We aimed to clarify whether SM loss and reduced GS have different associations with clinical characteristics and pancreatic imaging findings in patients with CP. METHODS: One hundred two patients with CP were enrolled. We defined SM loss by the SM index at the third lumbar vertebra on CT (<42 cm2/m2 for males and <38 cm2/m2 for females), and reduced GS by < 28 kg for males and <18 kg for females. RESULTS: Fifty-seven (55.9 %) patients had SM loss, 21 (20.6 %) had reduced GS, and 17 (16.7 %) had both. Patients with SM loss had lower body mass index, weaker GS, higher Controlling Nutritional Status score, lower serum lipase level, and lower urinary para-aminobenzoic acid excretion rate, suggesting worse nutritional status and pancreatic exocrine insufficiency. On CT, main pancreatic duct dilatation and parenchymal atrophy were more frequent in patients with SM loss than in those without it. Patients with reduced GS were older and had worse nutritional status than those without it. CONCLUSIONS: SM loss was associated with pancreatic exocrine insufficiency, low nutritional status, and pancreatic imaging findings such as parenchymal atrophy and main pancreatic duct dilatation, whereas older age and low nutritional status led to additional reduced GS.

A Novel Dry Simulator Model for Learning Comprehensive Endoscopic Retrograde Cholangiopancreatography/Endoscopic Sphincterotomy Procedures while Minimizing Adverse Bleeding Events (with Video).

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) are essential skills for performing endoscopic cholangiopancreatic procedures. However, these procedures have a high incidence of adverse events, and current training predominantly relies on patient-based approaches. Herein, we aimed to develop an ERCP/EST simulator model to address the need for safer training alternatives, especially for learners with limited ERCP experience. METHODS: The model was designed to facilitate the use of actual endoscopic devices, supporting learning objectives that align with the components of the validated Bethesda ERCP Skill Assessment Tool (BESAT). BESAT focuses on skills, such as papillary alignment, maintenance of duodenoscope position, gentle and efficient cannulation, controlled sphincterotomy in the correct trajectory, and guidewire manipulation. Thirty gastroenterology trainees used the simulator between May 2022 and March 2023, and their satisfaction was assessed using a visual analog scale (VAS) and pre- and post-training questionnaires. RESULTS: The novel simulator model comprised a disposable duodenal papillary section, suitable for incision with an electrosurgical knife, alongside washable upper gastrointestinal tract and bile duct sections for repeated use. The duodenal papillary section enabled reproduction of a realistic endoscope position and the adverse bleeding events due to improper incisions. The bile duct section allowed for the reproduction of fluoroscopic-like images, enabling learners to practice guidewire guidance and insertion of other devices. Following training, the median VAS score reflecting the expectation for model learning significantly increased from 69.5 (interquartile range [IQR]: 55.5-76.5) to 85.5 (IQR: 78.0-92.0) (p < 0.01). All participants expressed a desire for repeated simulator training sessions. CONCLUSIONS: This innovative simulator could serve as a practical educational tool, particularly beneficial for novices in ERCP. It could facilitate hands-on practice with actual devices, enhancing procedural fluency and understanding of precise incisions to minimize the risk of bleeding complications during EST.

Association Between the Presence of Coronary Artery Disease or Peripheral Artery Disease and Left Ventricular Mass in Patients Who Have Undergone Coronary Computed Tomography Angiography.

Background: Left ventricular mass (LVM) is a critical marker of future cardiovascular risk. We determined the association between LVM measured by coronary computed tomography angiography (CCTA) and the presence of coronary artery disease (CAD) or peripheral artery disease (PAD) in patients who had undergone CCTA for screening of CAD. Methods: We enrolled 1,307 consecutive patients (66 ± 12 years old, 49% males) who underwent CCTA for screening of CAD at the Fukuoka University Hospital (FU-CCTA registry), and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. Patients with coronary stenosis of ≥ 50% by CCTA were diagnosed as CAD. Patients with an ankle brachial pressure index < 0.9 or who had already been diagnosed with PAD were considered to have PAD. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were measured. The patients were divided into CAD (-) and CAD (+) or PAD (-) and PAD (+) groups. Results: The prevalences of CAD and PAD in all patients were 50% and 4.8%, respectively. Age, %males, %hypertension (HTN), %dyslipidemia (DL), %diabetes mellitus (DM), %smoking and %chronic kidney disease in the CAD (+) group were significantly higher than those in the CAD (-) group. Age, %males, %HTN, %DM and %smoking in the PAD (+) group were significantly higher than those in the PAD (-) group. CAD was independently associated with LVMI (odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01 - 1.02, P < 0.01) in addition to age, male, HTN, DL, DM, and smoking. PAD was also independently associated with LVMI (OR: 1.01, 95% CI: 1.0 - 1.02, P = 0.018) in addition to age, DM, and smoking. Conclusions: LVMI determined by CCTA may be useful for predicting atherosclerotic cardiovascular diseases including both CAD and PAD, although there were considerable differences between %CAD and %PAD in all patients.

Endoscopic nasobiliary drainage versus endoscopic biliary stenting for preoperative biliary drainage in patients with malignant hilar biliary obstruction: Propensity score-matched multicenter comparative study.

OBJECTIVES: For preoperative biliary drainage (PBD) of malignant hilar biliary obstruction (MHBO), current guidelines recommend endoscopic nasobiliary drainage (ENBD) due to the higher risk of cholangitis after endoscopic biliary stenting (EBS) during the waiting period before surgery. However, few studies have supported this finding. Therefore, we aimed to compare the outcomes of preoperative ENBD and EBS in patients with MHBO. METHODS: Patients with MHBO who underwent laparotomy for radical surgery after ENBD or EBS were included from retrospectively collected data from 13 centers (January 2014 to December 2018). We performed a 1:1 propensity score matching between the ENBD and EBS groups. These patients were compared for the following: cholangitis and all adverse events (AEs) after endoscopic biliary drainage (EBD) until surgery, time to cholangitis development after EBD, postsurgical AEs, and in-hospital death after surgery. RESULTS: Of the 414 patients identified, 355 were analyzed in this study (226 for ENBD and 129 for EBS). The matched cohort included 63 patients from each group. The proportion of cholangitis after EBD was similar between the two groups (20.6% vs. 25.4%, P = 0.67), and no significant difference was observed in the time to cholangitis development. The proportions of surgical site infections, bile leaks, and in-hospital mortality rates were similar between the groups. CONCLUSION: For PBD of MHBO, the proportion of AEs, including cholangitis, after EBD until surgery was similar when either ENBD or EBS was used.

Associations of High-Density Lipoprotein Functionality with Coronary Plaque Characteristics in Diabetic Patients with Coronary Artery Disease: Integrated Backscatter Intravascular Ultrasound Analysis.

High-density lipoprotein (HDL) functionality has been reported to be associated with coronary artery disease (CAD). However, little is known about the impact of HDL functionality on coronary atherosclerosis. Thirty-eight type 2 diabetic patients with CAD who underwent percutaneous coronary intervention were examined. Coronary atheroma burden and plaque composition of the culprit lesions were assessed using conventional gray-scale and integrated backscatter intravascular ultrasound. HDL-mediated cholesterol efflux capacity (HDL-CEC) and HDL antioxidant capacity, estimated as HDL inflammatory index (HII), were examined. The associations between HDL functionality and coronary plaques were analyzed using multivariate data analysis, including principal components analysis and orthogonal partial least squares (OPLS) models. Percent atheroma volume was correlated with HDL-CEC (r = 0.34, p = 0.04) but not with HII (p = 0.65). The OPLS model demonstrated that the percentage lipid volume was significantly associated with HDL functionality [coefficient (95% confidence interval); HDL-CEC: -0.26 (-0.49, -0.04); HII: 0.34 (0.08, 2.60), respectively]. HII exhibited the highest variable importance in projection score, indicating the greatest contribution. HDL functionality was associated with coronary plaque composition, a key component of plaque vulnerability. Our findings highlight the potential importance of HDL functionality for coronary plaque stabilization.

Association between Major Adverse Cardiovascular Events and the Liver Fibrosis Score in Patients with and without Coronary Artery Disease: From the FU-CCTA Registry.

The liver fibrosis score reflects the degree of hepatic scarring and has been reported to be associated with cardiovascular disease. Using a coronary artery computed tomography angiography registry at the Fukuoka University Hospital (FU-CCTA registry), we investigated the association between major adverse cardiovascular events (MACEs) and the liver fibrosis score (fibrosis-4 index (FIB-4I)) in 612 patients who underwent CCTA to screen for coronary artery disease and performed a prognosis survey for up to 5 years. The primary endpoint was MACEs (all-cause mortality, acute myocardial infarction, ischemic stroke, coronary revascularization). FIB-4I in all patients and in patients with hypertension (HTN) was significantly higher in the MACE group than in the non-MACE group. The event-free survival rate of MACEs targeting only patients with HTN was significantly lower in patients with a high risk of liver fibrosis (FIB-4I values of 2.67 or higher) than in those with a low or intermediate risk (less than 2.67). However, no significant difference was observed in all patients or in patients without HTN. Finally, FIB-4I and body mass index were independent factors associated with MACEs in patients with HTN. In conclusion, the liver fibrosis score may be an independent predictor of MACEs in hypertensive patients undergoing CCTA.

Association Between Telomere G-Tail Length and Coronary Artery Disease or Statin Treatment in Patients With Cardiovascular Risks　- A Cross-Sectional Study.

Background: The utility of telomere G-tail length to predict coronary artery disease (CAD) remains controversial. CAD results from coronary artery narrowing due to cholesterol and lipid accumulation, augmented by inflammatory cells and other factors. This study explored the significance of telomere G-tail length in suspected CAD patients. Methods and Results: In all, 95 patients with suspected CAD or ≥1 cardiac risk factor underwent coronary computed tomography angiography (CCTA). We measured leukocyte telomere length and G-tail length using a hybrid protection method, and diagnosed the presence of CAD using CCTA. Associations between G-tail length and the presence of CAD, the number of stenosed coronary arteries, and brachial-ankle pulse wave velocity (baPWV) were analyzed. No significant difference was observed in G-tail length when comparing groups with or without CAD or statin treatment. However, in the non-statin group, G-tail length was significantly shorter in patients with 3-vessel disease compared with 1-vessel disease. Dividing the group using a baPWV of 1,300 cm/s, telomere G-tail length was significantly shorter in the high-risk (baPWV ≥1,300 cm/s) group. Conclusions: The clinical utility of telomere G-tail length as a CAD risk indicator seems limited. There was a trend for longer telomere G-tail length in the statin-treated group. Moreover, telomere G-tail length was reduced in patients at high-risk of cardiovascular events, aligning with the trend of a shortening in telomere G-tail length with CAD severity.

Association between paroxysmal or persistent atrial fibrillation and hyperuricemia in patients who underwent coronary computed tomography angiography: from the FU-CCTA-AF Registry.

BACKGROUND: Hyperuricemia (HU) and hypertension (HTN) contribute to atherosclerotic cardiovascular disease, and both are also involved in the onset and development of atrial fibrillation (AF). OBJECTIVE: In the present study, we investigated the association between risk factors for atherosclerosis [including HU, HTN, blood pressure and serum uric acid (UA) levels] and paroxysmal atrial fibrillation (Paro-AF) or persistent atrial fibrillation (Pers-AF) in patients who underwent coronary computed tomography angiography (CCTA). METHODS: We enrolled 263 patients from the Fukuoka University-CCTA-AF (FU-CCTA-AF Registry) who underwent CCTA prior to AF ablation therapy. AF was classified as either Paro-AF (≤ 7 days) or Pers-AF (> 7 days). HU was diagnosed by a serum UA level > 7.0 mg/dl, and coronary artery disease (CAD) was diagnosed when CCTA results showed ≥ 50% significant coronary artery stenosis. The number of significantly diseased coronary artery vessels (VD), the Gensini score and the coronary artery calcification score (CACS) were measured. Left atrial morphology was also evaluated. RESULTS: Diastolic blood pressure and HbA1c in the Pers-AF group were significantly higher than those in the Paro-AF group. The Pers-AF group showed a significantly higher prevalence of HU and higher UA levels than the Paro-AF group. In a multivariate logistic regression analysis, HU was an independent associated factor to Pers-AF (odds ratio: 2.023, 95% confidence interval: 1.055-3.881, p = 0.034), while HTN was not. CONCLUSION: In patients with AF, HU is associated with Pers-AF.

Evaluation of the efficacy and safety of an integrated telerehabilitation platform for home-based cardiac REHABilitation in patients with heart failure (E-REHAB): protocol for a randomised controlled trial.

INTRODUCTION: Cardiac rehabilitation (CR) is strongly recommended as a medical treatment to improve the prognosis and quality of life of patients with heart failure (HF); however, participation rates in CR are low compared with other evidence-based treatments. One reason for this is the geographical distance between patients' homes and hospitals. To address this issue, we developed an integrated telerehabilitation platform, RH-01, for home-based CR. We hypothesised that using the RH-01 platform for home-based CR would demonstrate non-inferiority compared with traditional centre-based CR. METHODS AND ANALYSIS: The E-REHAB trial aims to evaluate the efficacy and safety of RH-01 for home-based CR compared with traditional centre-based CR for patients with HF. This clinical trial will be conducted under a prospective, randomised, controlled and non-inferiority design with a primary focus on HF patients. Further, to assess the generalisability of the results in HF to other cardiovascular disease (CVD), the study will also include patients with other CVDs. The trial will enrol 108 patients with HF and 20 patients with other CVD. Eligible HF patients will be randomly assigned to either traditional centre-based CR or home-based CR in a 1:1 fashion. Patients with other CVDs will not be randomised, as safety assessment will be the primary focus. The intervention group will receive a 12-week programme conducted two or three times per week consisting of a remotely supervised home-based CR programme using RH-01, while the control group will receive a traditional centre-based CR programme. The primary endpoint of this trial is change in 6 min walk distance. ETHICS AND DISSEMINATION: The conduct of the study has been approved by an institutional review board at each participating site, and all patients will provide written informed consent before entry. The report of the study will be disseminated via scientific fora, including peer-reviewed publications and presentations at conferences. TRIAL REGISTRATION NUMBER: jRCT:2052200064.

Development of Machine Learning-Based Web System for Estimating Pleural Effusion Using Multi-Frequency Bioelectrical Impedance Analyses.

BACKGROUND: Transthoracic impedance values have not been widely used to measure extravascular pulmonary water content due to accuracy and complexity concerns. Our aim was to develop a foundational model for a novel system aiming to non-invasively estimate the intrathoracic condition of heart failure patients. METHODS: We employed multi-frequency bioelectrical impedance analysis to simultaneously measure multiple frequencies, collecting electrical, physical, and hematological data from 63 hospitalized heart failure patients and 82 healthy volunteers. Measurements were taken upon admission and after treatment, and longitudinal analysis was conducted. RESULTS: Using a light gradient boosting machine, and a decision tree-based machine learning method, we developed an intrathoracic estimation model based on electrical measurements and clinical findings. Out of the 286 features collected, the model utilized 16 features. Notably, the developed model demonstrated high accuracy in discriminating patients with pleural effusion, achieving an area under the receiver characteristic curves (AUC) of 0.905 (95% CI: 0.870-0.940, p < 0.0001) in the cross-validation test. The accuracy significantly outperformed the conventional frequency-based method with an AUC of 0.740 (95% CI: 0.688-0.792, and p < 0.0001). CONCLUSIONS: Our findings indicate the potential of machine learning and transthoracic impedance measurements for estimating pleural effusion. By incorporating noninvasive and easily obtainable clinical and laboratory findings, this approach offers an effective means of assessing intrathoracic conditions.

Investigating the Association between Coronary Artery Disease and the Liver Fibrosis-4 Index in Patients Who Underwent Coronary Computed Tomography Angiography: A Cross-Sectional Study.

Liver fibrosis scores, indicative of hepatic scarring, have recently been linked to coronary artery disease (CAD). We investigated the association between CAD and the fibrosis-4 index (FIB-4I) in patients who underwent coronary computed tomography angiography (CCTA). This study included 1244 patients who were clinically suspected of having CAD. The presence or absence of CAD was the primary endpoint. FIB-4I was higher in the CAD group than in the non-CAD group (1.95 ± 1.21 versus [vs.] 1.65 ± 1.22, p < 0.001). FIB-4I was also higher in the hypertension (HTN) group than in the non-HTN group (1.90 ± 1.32 vs. 1.60 ± 0.98, p < 0.001). In all patients, high FIB-4I (≥2.67) was a predictor of presence of CAD (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.30-2.83, p = 0.001), and low FIB-4I (≤1.29) was proven to be a predictor of absence of CAD (OR: 0.65, 95% CI: 0.48-0.88, p = 0.006). In the HTN group, high and low FIB-4I levels, were found to be predictors for CAD (OR: 2.01, 95% CI: 1.26-3.21, p < 0.001 and OR: 0.65, 95% CI: 0.45-0.94, p < 0.022, respectively), in particular. FIB-4I may serve as a diagnostic indicator of the presence or absence of CAD in hypertensive patients undergoing CCTA.

Development of a Non-Peptide Angiotensin II Type 1 Receptor Ligand by Structural Modification of Olmesartan as a Biased Agonist.

As a biased agonist, peptide angiotensin II (Ang II) type 1 (AT1) receptor ligand antagonizes Ang II-stimulated G protein signaling but stimulates several kinase pathways. Here, we developed a non-peptide AT1 receptor compound as a biased ligand. We synthesized three non-peptide AT1 receptor ligands (R239470, R781253, and R794847) as candidates of biased ligands. Extracellular signal-regulated kinase (ERK) 1/2 activation and inositol phosphate (IP) production were measured using a cell system that overexpressed AT1 receptors (wild-type, L112A, Q257A, Y292A, and N295A receptors). We also examined the modes of receptor-ligand binding using a competition binding study. The Kd values of R239470, R781253, and R794847 for the AT1 wild-type receptor were 0.8, 21, and 48 nM, respectively, as assessed in a competition binding study. Those of R239470, R781253, and R794847 for the L112A receptor were 37, 23, and 31 nM, respectively. R781253 and R794847 decreased and increased IP production, respectively, whereas R239470 did not change IP production. R781253 and R794847, but not R239470, activated ERK1/2. In conclusion, R239470, R781253, and R794847 act as a neutral antagonist, an inverse agonist, and an agonist with regard to IP production, respectively. On the other hand, R781253 and R794847, but not R239470, are agonists toward ERK1/2 activation. Thus, we developed a non-peptide AT1 receptor compound as a biased ligand.

Association Between Major Adverse Cardiovascular Events and the Gensini Score or Coronary Artery Calcification Score in Hypertensive Patients Who Have Undergone Coronary Computed Tomography Angiography.

Background: From the Fukuoka University Coronary Computed Tomography Angiography (FU-CCTA) registry, we present major adverse cardiovascular events (MACEs) in hypertensive patients who have undergone CCTA, and the association between MACEs and the Gensini score of coronary arteries or the coronary artery calcification (CAC) score. Methods: Of the patients who underwent CCTA for coronary artery disease (CAD) screening at Fukuoka University Hospital, 318 hypertensive patients who had at least one cardiovascular risk factor or suspected CAD were enrolled. The patients were divided into two groups: MACEs and non-MACEs groups. The severity of atherosclerosis of coronary arteries was assessed by the Gensini score. The CAC score was also defined by computed tomography (CT) images at the time of CCTA. A primary endpoint was MACEs (all-cause death, ischemic stroke, acute myocardial infarction, coronary revascularization). The patients were followed for up to 5 years. Results: The patients were 68 ± 10 years, and 50% were males. The percentages of smoking, dyslipidemia, diabetes, and chronic kidney disease were 39%, 70%, 26% and 37%, respectively. The %males, %smoking, CAC score and Gensini score in the MACEs group were significantly higher than those in the non-MACEs group. On the other hand, the differences in age, dyslipidemia, diabetes, or chronic kidney disease between the groups were not seen. A multivariate analysis was performed regarding the presence or absence of MACE by logistic regression analysis of the CAC score or Gensini score in addition to conventional risk factors as independent variables. A Cox regression analysis revealed significant relationships for both the CAC score (P = 0.043) and the Gensini score (P = 0.008). Conclusions: The CAC score and the Gensini score could predict MACEs in hypertensive patients who have undergone CCTA.